Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute , The University of Chicago , Chicago , Illinois 60637 , United States.
Center for Molecular Engineering and Materials Science Division , Argonne National Laboratory , Lemont , Illinois 60439 , United States.
Biomacromolecules. 2019 Sep 9;20(9):3385-3391. doi: 10.1021/acs.biomac.9b00621. Epub 2019 Aug 19.
Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.
一些合成聚合物在损伤后应用时可以阻止细胞死亡，否则细胞会死亡。这种细胞拯救是通过聚合物与细胞膜的相互作用实现的。然而，设计确保强但非破坏性的细胞膜靶向的合成聚合物的一般原则尚未完全阐明。在这里，我们根据仿生含磷酰胆碱的嵌段共聚物与细胞膜相互作用，并确定它们在阻断氧葡萄糖剥夺后神经元死亡的功效。通过调整基于聚（2-甲基丙烯酰氧基乙基磷酰胆碱）（聚 MPC）的三嵌段共聚物的亲水性和膜亲和力，确定了共聚物有效地作为膜靶向细胞拯救剂发挥作用的表面活性剂体系。我们发现聚合物与细胞膜之间存在非侵入性相互作用，通过诱导刚性化而不破坏脂质堆积或膜厚度来改变膜的集体动力学。总的来说，我们的结果为基于聚 MPC 的聚合物的生物应用开辟了新的途径，并提供了一种设计用于阻断损伤后细胞死亡的靶向细胞膜的试剂的方法。
